Interspecies variations in fatty acid hydroxylations involving cytochromesP450 2E1 and 4A

The liver microsomal fractions of seven mammalian species including rat, do g, monkey, hamster, mouse, gerbil and humans, catalyzed the hydroxylation o f saturated (lauric, myristic and palmitic) and unsaturated (oleic and lino leic) fatty acids to the corresponding omega and (omega-1)-hydroxylated der ivatives, while stearic acid was not metabolized. Lauric acid was the most efficiently hydroxylated, and the rank of catalytic activity was lauric > m yristic > oleic > palmitic > linoleic. Among the mammalian species studied, mouse and hamster presented the highest level of fatty acid omega and (ome ga-1)-hydroxylases, while the lowest activity was observed in dog and monke y. In all the animal species, the (omega-1)-hydroxylation of fatty acids co rrelated significantly with the immunodetectable content of CYP2E1 and the 4-nitrophenol hydroxylation activity, known to be mediated by cytochrome P4 50 2E1. On the contrary, only the omega-hydroxylation of lauric acid slighl y correlated with the level of cytochrome P450 4A, while no significant cor relation was found with the omega-hydroxylation of the other fatty acids. F urthermore, chemical and immune-inhibitions of the hydroxylations of fatty acids led to the conclusion that fatty acid (omega-1)-hydroxylase activity is catalyzed by P450 2E1 in all the mammalian species, while the fatty acid omega-hydroxylase activity may be catalyzed by cytochromes P450 from the 4 A family. Therefore, lauric acid (omega-1)-hydroxylation along with 4-nitro phenol hydroxylation can be used as a specific and sensitive method to meas ure the level of CYP2E1 induction in humans and various animals. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.